含美罗华联合方案治疗复发耐药B细胞性非霍奇金淋巴瘤

背景与目的:复发或耐药的B细胞性非霍奇金淋巴瘤(non-Hodgkin slymphoma,NHL)预后不良,二线方案化疗远期生存差;抗CD20单克隆抗体美罗华(rituximab)与CHOP或类似方案联合作为一线方案治疗初治侵袭性淋巴瘤可提高远期生存率,但在二线治疗中的作用尚未确定。本研究初步探讨含美罗华联合方案治疗复发耐药B细胞性NHL的近期疗效和不良反应的情况。方法:中山大学肿瘤防治中心近年应用含美罗华方案治疗35例复发耐药NHL患者,其中男性19例,女性16例,中位年龄53.5岁。PS评分0～1分33例(94.3%)。IPI评分0～1分20例(57.1%),2分7例(20.0%),3分4例(11.4%),4～5分4例(11.4%);病理类型以弥漫大B细胞性为主(23例,占65.7%)。所有患者都接受含美罗华的治疗,每疗程前1天应用,剂量375mg/m2,二、三线挽救化疗方案包括EPOCH、CHOP、DHAP、DICE、IMVP-16和FND等。结果:35例患者中单用美罗华治疗者5例,美罗华联合化疗30例,共化疗102疗程。32例可评价客观疗效,有效率68.8%(22/32),完全缓解(CR)13例(40.6%),3例患者在含美罗华方案治疗后接受局部放疗获CR,3例患者在挽救方案治疗后加用造血干细胞移植获CR。主要不良反应为胃肠道反应、骨髓抑制、脱发等,加用美罗华治疗主要增加畏寒、发热等输注相关反应(5例)。中位随访时间12.5个月(3～69个月),失访2例,全组死亡10例(9例死于疾病进展,1例死于重症乙型性肝炎),中位无进展生存期(PFS)11.8个月(3～33个月)。总的1、2、3年生存率分别为72.9%、62.8%和62.8%。结论:含美罗华方案治疗复发耐药的B细胞NHL有效率高、不良反应可以耐受,值得在更大宗病例中作进一步研究。     

一例难治性慢性淋巴细胞白血病患者的循证治疗

目的采用循证实践的方法指导难治性慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)的临床治疗。方法针对1例CLL患者的病情,计算机检索Cochrane图书馆(2010年第10期)、OVID、PubMed(1992.1～2010.10)、美国国家综合癌症网络网站(http://www.nccn.org/)等循证医学的三级文献数据库,查找高质量临床证据,并根据患者意愿为患者制定最佳治疗方案。结果共纳入2个RCT,5个CCT。现有临床证据显示:①对于难治性CLL,美罗华(利妥昔单抗)能进一步改善联合化疗的疗效。②对于氟达拉滨耐药的CLL,COP/CHOP方案仍然有效。③造血干细胞移植仍为复发/难治CLL的有效挽救治疗方案,但尚无依据支持其成为一线选择。采用美罗华联合CHOP方案治疗该患者,停化疗2月后复查显示病情缓解,目前仍在随访中。结论现有证据表明美罗华联合CHOP方案耐受性好,疗效优于单用CHOP方案,本例临床实践结果也显示接受美罗华联合CHOP方案的患者的预后较好,但仍需高质量证据进一步验证。     

Rituximab (Anti-cd20 Monoclonal Antibody) in Children with Chronic Refractory Symptomatic Immune Thrombocytopenic Purpura: Efficacy and Safety of Treatment

This retrospective study investigated the effects of rituximab in 19 pediatric patients (15 girls and 4 boys) with chronic refractory symptomatic immune thrombocytopenic purpura (ITP). Patients received from 2 to 5 weekly infusions of rituximab (375 mg/m(2)); 15 patients were younger than 12 years when treated. The median follow-up time was 30 months (range, 9-43 months). The overall response rate was 68% (13/19 patients). Six responders relapsed at a median of 4.5 months (range, 3-8 months). Seven patients still displayed a platelet count >150,000/microL at a median of 33 months (range, 14-43 months) after rituximab treatment. Six of 15 patients treated with 4 or 5 weekly infusions and 1 of 4 patients treated with 2 or 3 infusions are still in remission. No difference was detected between splenectomized and nonsplenectomized patients. The duration of ITP disease at the time of treatment did not influence the response rate. Patients still in remission showed significantly lower levels of CD19+ cells after 4 and 6 months than nonresponding or relapsed patients (P < .05). No major infections were reported during follow-up. Our data show the efficacy and tolerability of rituximab in young children with refractory symptomatic ITP. Nonrelapsed patients showed a more prolonged B-cell depletion.     

A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus

Although corticosteroids and immunosuppressants are widely used for the treatments of systemic lupus erythematosus (SLE), safer and more effective therapies are prerequisite. We and others have reported that anti-CD20 antibody rituximab targeting B cells are effective for refractory SLE and, therefore, safety and clinical efficacy of rituximab in SLE was evaluated by a multicenter phase I/II clinical trial. An open-label, multicenter study of 15 patients with active and refractory SLE (total British Isles Lupus Assessment Group [BILAG] score 8 to 17) was conducted. Rituximab was administered to 5 SLE patients as 4 infusions of 500 mg/body every week and to 10 SLE patients as 2 infusions of 1000 mg/body every other week. Assessment of safety, infusion reactions and adverse effects was used as the primary outcome for clinical tolerability and was evaluated by 28 weeks. Rituximab was well tolerated, with most experiencing no significant adverse effects. B cells rapidly reduced in all patients and remained low until 6 months post-treatment. Four patients developed human antichimeric antibodies without affecting efficacy of rituximab. Changes in routine safety laboratory tests clearly related to rituximab were not observed. Nine among 14 evaluable patients achieved the major or partial clinical response of BILAG score and prednisolone dose significantly decreased at the 28 weeks. Rituximab therapy appears to be safe for the treatment of active SLE patients and holds significant therapeutic promise, at least for the majority of patients experiencing profound B-cell depletion.     

Treatment of refractory retrobulbar granuloma with rituximab in a patient with ANCA-negative Wegener’s granulomatosis: a case report

Retrobulbar granuloma is one of the serious complications in Wegener’s granulomatosis and often shows resistance to conventional therapy during long-term treatment. The outcome of this complication includes visual loss, orbital and facial deformity, fistula formation, as well as infection. There has been increasing evidence that shows the efficacy of rituximab, a chimeric anti-B cell mAb, for the treatment of autoimmune diseases including Wegener’s granulomatosis. We present a 22-year-old Japanese woman who was diagnosed with Wegener’s granulomatosis complicated by refractory retrobulbar granuloma. She was admitted to our hospital with pain of the right eye and right proptosis during treatment with monthly IVCY for Wegener’s granulomatosis. We diagnosed refractory retrobulbar granuloma by computed tomography (CT) scan and biopsy. She showed a refractory growth of retrobulbar granuloma in spite of negative ANCA. She was also complicated with pulmonary granulomatous lesions in bilateral apices. After approval by an institutional ethical committee and informed consent of this patient, rituximab 375 mg/m² was intravenously administered weekly four times. Concomitant prednisolone 0.5 mg/kg was also administered for 2 weeks and gradually tapered. Treatment of rituximab resulted in prompt relief of symptoms in this case and the reduction of the granuloma. BVAS score also improved from 6 to 0 at 3 months and was kept in remission for 12 months. Circulating CD19-positive cells were kept less than 0.1% during the follow-up. There were no serious adverse events. This case suggests that rituximab is effective for refractory retrobulbar granuloma complicated in Wegener’s granulomatosis even when ANCA titers are negative.     

利妥昔单抗对儿童高分期成熟B细胞非霍奇金淋巴瘤的疗效研究

目的探讨儿童高分期、成熟B细胞非霍奇金淋巴瘤标准化疗联合利妥昔单抗治疗的的有效性和安全性。方法收治儿童非霍奇金淋巴瘤62例,为St.Jude分期Ⅲ～Ⅳ的患者,35例采用法国儿童肿瘤协会系列研究(lymphomes malins B,LMB)89方案,27例采用LMB89联合利妥昔单抗治疗方案,分析两组患儿的临床资料特征、治疗效果,Kaplan-Meier方法进行生存分析。结果原发部位、病理诊断、临床分期、乳酸脱氢酶≥2ULN者和骨髓和(或)中枢神经受累等参数两组相比均无统计学差异(P>0.05)。治疗后,LMB89组中有5例继发感染,LMB89+利妥昔单抗组为8例,差异无统计学意义(P>0.05)。两组发生肿瘤溶解综合征的患儿例数分别为4例和2例,差异无统计学意义(P>0.05)。LMB89组在化疗过程中出现肝功能受损1例,肠穿孔1例。LMB89+利妥昔单抗组出现肝功能受损1例,两组化疗出现并发症总数相比无统计学意义(P>0.05)。LMB89组5年无事件生存率为68.8%,5年总生存率为62.9%,LMB89+利妥昔单抗组5年的无事件生存率为92.6%,5年总...     

Rituximab for sight-threatening refractory pediatric Vogt–Koyanagi–Harada disease

Rituximab was trialed in a refractory Vogt–Koyanagi–Harada disease (VKH). A 10-year-old girl with panuveitis recalcitrant to treatment, including corticosteroids, was diagnosed with VKH 20 months later. Following rituximab at 0, 1, 6, and 18 months, response was favorable after the second dose, usual life activity resumed after the third dose (uveitis was inactivated and vision improved), and eyes stabilized 9 months after the fourth dose. Rituximab is effective in the treatment and long-term control of advanced, pediatric VKH.     

Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis

Objective

To evaluate the efficacy and safety of rituximab for relapsing-remitting multiple sclerosis.

HLA-C Matching Status Does Not Affect Rituximab-Mediated Antibody-Dependent Cellular Cytotoxicity by Allogeneic Natural Killer Cells

Risk of leukemia relapse after T cell-depleted hematopoietic stem cell transplantation is lower in the “HLA-C mismatched” recipient-donor combinations. This might be attributable to increased natural killing by allogeneic NK cells carrying a KIR that does not bind to HLA-C on target cells (HLA-C-uncoupled KIR). Considering a new strategy of allogeneic NK cell transfer with rituximab to treat B-cell lymphomas, however, it is unknown whether the HLA-C matching status also affects rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC). To address this issue, we investigated the levels of ADCC by purified NK cells carrying an HLA-C-uncoupled KIR, where the NK cell donors had either matched or mismatched HLA-C combination with target cells. Purified NK cells carrying an HLA-C-uncoupled KIR consistently showed enhanced ADCC against target cells when NK cell donors had an HLA-C-mismatch. When NK cell donors did not have an HLA-C mismatch, it was inconsistent whether HLA-C-uncoupled KIR caused ADCC enhancement. When the levels of ADCC by whole NK cells were compared, there were substantial differences among the donors regardless of the HLA-C matching status. Subjects with HLA-C mismatch may not have an advantage when cytoimmunotherapy using allogeneic NK cells is considered in combination with rituximab.